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Histone modification induced by alpha-synuclein

Research Project

Project/Area Number 17K09745
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionTohoku University

Principal Investigator

Sugeno Naoto  東北大学, 大学病院, 助教 (30509550)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsパーキンソン病 / エピジェネティクス / αーシヌクレイン / αシヌクレイン / ヒストン修飾 / 神経分化 / 免疫沈降 / クロマチン免疫沈降 / alpha-synuclein
Outline of Final Research Achievements

Alpha-synuclein (aS) is a key molecule to understand pathomechanisms underlying Parkinson’s disease. Physiological intracellular localization of aS is mainly pre-synaptic membrane, but a part of aS reside nucleus. We focused on the function of aS in nucleus, especially in epigenomic regulation of neuronal genes. At the first step of this project, we tried to find out the aS-interacting proteins in nucleus, and successfully achieved because some of the components of BAF complex that actively work during neuronal differentiation, were significantly bonded with aS. Also, the enzyme that catalyzes histone methylation was also involve in this complex. Interestingly, altered histone modification targeted by the enzyme was enhanced by aS expression in differentiated SH-SY5Y cells. Finally, we identified some neuronal genes affected by the histone methylation.

Academic Significance and Societal Importance of the Research Achievements

パーキンソン病発症の最大のリスクは加齢であり、現在進行中の高齢化社会において本疾患への対応は急務となっている。ドパミン補充療法が運動機能改善に役立つものの、一方でドパミン製剤による衝動制御障害は罹患者の生活を破壊しうるものであり発生を未然に防ぐ必要がある。本研究ではαシヌクレインを出発点とした分子生物学的アプローチにより、衝動制御障害のリスクとなりうる遺伝子の発現変化が導かれることを見出した。今後、実臨床へと発展させることにより衝動制御障害のリスクを事前に知ることが可能となると思われる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (13 results)

All 2019 2018 2017

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (7 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Unveiling the coupling of flotillin-1 and extracellular α-synuclein: relevance to dopamine transporter trafficking and Lewy body formation2019

    • Author(s)
      Kobayashi J, Hasegawa T, Sugeno N, Yoshida S, Miki Y, Fukuda M, Kawahata I, Yamakuni T, Tomiyama A, Kawata Y, Ezura M, Kikuchi A, Baba T, Wakabayashi K, Takeda A, Aoki M
    • Journal Title

      FASEB Journal

      Volume: 33 Issue: 9 Pages: 10240-10256

    • DOI

      10.1096/fj.201802051r

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Longitudinal changes in 18F-THK5351 PET in corticobasal syndrome2019

    • Author(s)
      Ezura M, Kikuchi A, Ishiki A, Okamura N, Hasegawa T, Harada R, Watanuki S, Funaki Y, Hiraoka K, Baba T, Sugeno N, Oshima R, Yoshida S, Kobayashi J, Kobayashi M, Tano O, Nakashima I, Mugikura S, Iwata R, Taki Y, Furukawa K, Arai H, Furumoto S, Tashiro M, Yanai K, Kudo Y, Takeda A, Aoki M
    • Journal Title

      Eur J Neurol

      Volume: 26 Issue: 9 Pages: 1205-1211

    • DOI

      10.1111/ene.13966

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Parkinson’s disease-linked DNAJC13 mutation aggravates α-synuclein-induced neurotoxicity through perturbation of endosomal trafficking.2018

    • Author(s)
      Yoshida S, Hasegawa T, Suzuki M, Sugeno N, Kobayashi J, Ueyama M, Fukuda M, Ido-Fujibayashi A, Sekiguchi K, Ezura M, Kikuchi A, Baba T, Takeda A, Mochizuki H, Nagai Y and Aoki M.
    • Journal Title

      Hum Mol Genet.

      Volume: 27 Issue: 5 Pages: 823-836

    • DOI

      10.1093/hmg/ddy003

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] DnaJ/Hsp40 family and Parkinson’s disease.2018

    • Author(s)
      Hasegawa T, Yoshida S, Sugeno N, Kobayashi J, Aoki M.
    • Journal Title

      Front Neurosci

      Volume: 11 Pages: 743-743

    • DOI

      10.3389/fnins.2017.00743

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Membrane Trafficking Illuminates a Path to Parkinson’s Disease2017

    • Author(s)
      Hasegawa T, Sugeno N, Kikuchi A, Baba T, Aoki M.
    • Journal Title

      The Tohoku Journal of Experimental Medicine

      Volume: 242 Issue: 1 Pages: 63-76

    • DOI

      10.1620/tjem.242.63

    • NAID

      130005679072

    • ISSN
      0040-8727, 1349-3329
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Hot Topics 01: Molecular and cellular basis of neurotoxicity caused by α-synuclein2019

    • Author(s)
      Sugeno N
    • Organizer
      第59回日本神経学会学術大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Alpha-synuclein interacts with BAF complex in nucleus2019

    • Author(s)
      Sugeno N, Hasegawa T, Kobayashi J, Yoshida S, Ezura M, Kikuchi A, Takeda A, Aoki M.
    • Organizer
      The 5th World Parkinson Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Alpha-synuclein interacts with BAF complex in nucleus2019

    • Author(s)
      Sugeno N, Hasegawa T, Kobayashi J, Yoshida S, Ezura M, Kikuchi A, Takeda A, Aoki M.
    • Organizer
      International Congress of Parkinson’s Disease and Movement Disorders
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Alpha-synuclein interacting protein in nucleus2018

    • Author(s)
      Naoto Sugeno, Takafumi Hasegawa, Junpei Kobayashi, Shun Yoshida, Michinori Ezura, Akio Kikuchi, Atsushi Takeda, Masashi Aoki
    • Organizer
      第59回日本神経学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Alpha-synuclein interacts with BAF complex in nucleus2018

    • Author(s)
      Naoto Sugeno, Takafumi Hasegawa, Junpei Kobayashi, Shun Yoshida, Michinori Ezura, Akio Kikuchi, Atsushi Takeda, Masashi Aoki
    • Organizer
      第12回パーキンソン病・運動障害疾患コングレス
    • Related Report
      2018 Research-status Report
  • [Presentation] Alpha-synuclein enhances histone H3 lysine-9 dimethylation2017

    • Author(s)
      Naoto Sugeno, Sandra Jackel, Aaron Voigt, Philipp Kahle
    • Organizer
      International Congress of Parkinson's Disease and Movement Disorders
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] α-シヌクレイン核内結合タンパクの探索2017

    • Author(s)
      菅野 直人、長谷川 隆文、小林 潤平、吉田 隼、江面 道典、菊池 昭夫、武田 篤、青木 正志
    • Organizer
      MDSJ
    • Related Report
      2017 Research-status Report
  • [Book] 運動失調のみかた,考えかた III-8 プリオン仮説2017

    • Author(s)
      菅野 直人、長谷川 隆文
    • Total Pages
      358
    • Publisher
      中外医学社
    • ISBN
      9784498228900
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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